A lethal dose of caffeine is thought to be roughly 10 grams — about the mass of your standard #2 pencil. That converts to a whopping (but basically undrinkable) 4.69 gallons of coffee, or 120 standard cans of Red Bull. Still, 2012 saw several deaths linked to energy drinks in the United States — five were attributed to Monster Energy drinks and thirteen to 5-hour Energy shots. These came on top of a massive spike in energy-drink associated ER visits. Caffeine's harmful or unwanted effects can be triggered at much lower doses than what is considered "toxic." So how much caffeine is too much?

Caffeine gets cleared from the body at different rates because of genetic variations, gender, and even whether a person is a smoker. For this reason, it's difficult to set a safe limit of daily consumption on the compound. Physiological differences, as well as differences in the way people consume caffeine, have tied FDA in knots as it has debated how to regulate the substance.

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In the end we know that the caffeine content in something like five ounces of coffee isn't going to kill you, and that five gallons probably will. But what about everything in between? To reiterate Wolf's point: everyone processes caffeine differently, and every person brings his or her own metabolism, medical history and genetic factors to the table — so setting a catchall "safety limit" is easier said than done.

Not that people haven't tried. Writes Wolf (emphasis added):

In 2003, a team at Health Canada, a government regulatory agency, reviewed more than 200 studies about caffeine's effects on human health. On the basis of the survey, the team concluded that 400 mg of caffeine per day (or about three 8-oz cups of brewed coffee) is a safe dose for healthy adults to consume. At and below this level, the average person does not experience negative mood changes or heart problems, the report stated.

Of course, caveats to this finding abound. One that sticks out immediately ties back to what we mentioned earlier about the perils of caffeinating while pregnant. One of the more recent studies to examine this risk was published in 2008 in the American Journal of Obstetrics and Gynecology, and concluded that the risk of miscarriage is more than double in women who consume over 200 mg of caffeine per day. That's half the limit proposed by the Health Canada team. As a point of reference, a 2-oz shot of 5-Hour Energy contains 215 mg of caffeine, a can of Monster ~260 mg.

200 mg/day is also the upper caffeine limit recommended by the American College of Obstetricians and Gynecologists. According to Wolf, women on the pill break down caffeine slower than those who aren't, and smokers clear it from their bodies more quickly than non-smokers. "The Health Canada team also recommended a limit of 2.5 mg per kg body weight per day for children," notes Wolf. "For an average 10-year-old in the U.S., that's about 75 mg of caffeine, or two 12-oz cans of Coca-Cola."

The wide range of Individual caffeine sensitivities has kept the FDA from recommending any definitive consumption limit. "Experts agree that 600 mg (four to seven cups of coffee) of caffeine or more each day is too much," reads this leaflet from the Agency. That's more than you'll find in any given beverage, but then again, who among us drinks one cup of morning coffee and thinks gee, I think that's probably enough?

One of the biggest hurdles consumers face in gauging their caffeine consumption is the lack of oversight by the FDA on products like Monster and 5-Hour Engergy. Via the New York Times:

The F.D.A. has stated that it does not have sufficient scientific evidence to justify changing how it regulates caffeine or other ingredients in energy products. The issue of how to do so is complicated by the fact that some high-caffeine drinks, like Red Bull, are sold under agency rules governing beverages, while others, like 5-Hour Energy and Monster Energy, are marketed as dietary supplements. The categories have differing ingredient rules and reporting requirements.

In order for the FDA to intervene, the agency needs to demonstrate that there exists "a significant or reasonable risk of illness or injury under the normal conditions of use or in the labeling," according to Daniel Fabricant, director of FDA's Division of Dietary Supplement Programs. But that evidence doesn't exist.

Or rather, it doesn't yet. According Wolf, there have been five reported deaths and 30 adverse events possibly linked to Monster Energy since 2008 — incidents the FDA claims to be taking very seriously.

For tons more info — including fascinating new findings on the role of genetics in individual response to caffeine, check out Wolf's piece in the latest issue of C&EN.